Frequency of hereditary hemochromatosis gene mutations and their effects on iron overload among beta thalassemia patients of Chennai residents

Bhuvana Selvaraj; Sangeetha Soundararajan; Shettu Narayanasamy; Ganesan Subramanian; Senthil Kumar Ramanathan; Bhuvana Selvaraj; Sangeetha Soundararajan; Shettu Narayanasamy; Ganesan Subramanian; Senthil Kumar Ramanathan

doi:10.3934/molsci.2021018

AIMS Molecular Science

2021, Volume 8, Issue 4: 233-247. doi: 10.3934/molsci.2021018

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Research article

Frequency of hereditary hemochromatosis gene mutations and their effects on iron overload among beta thalassemia patients of Chennai residents

1.
Department of Molecular Biology, Dr. Ganesan's Hitech Diagnostic centre, Chennai, Tamil Nadu, India
2.
PG and Research Department of Zoology, Pachaiyappa's College, University of Madras, Chennai, Tamil Nadu, India
3.
Department of Pathology, Dr. Ganesan's Hitech Diagnostic centre, Chennai, Tamil Nadu, India
4.
Department of Molecular Biology, Dr. Ganesan's Hitech Diagnostic centre, Chennai, Tamil Nadu, India

Received: 09 September 2021 Accepted: 09 November 2021 Published: 12 November 2021

Hereditary Hemochromatosis (HH) is an autosomal recessive disorder of iron metabolism associated with HFE gene mutations, characterized by increased iron absorption and accumulation leading to multi-organ damage caused by iron overload toxicity. Beta thalassemia is caused by a mutation in the human beta globin gene. Imbalanced production of globin chain results in beta thalassemia, where the unpaired alpha chains precipitates in red cell precursors leading to ineffective erythropoiesis and reduced RBC survival. Both HH and beta thalassemia condition results in rapid accumulation of iron lead to iron overload in tissues and organs. The study aims to analyze the frequency of HFE variants among beta thalassemia cases and their effect on iron overload. The frequency of three HFE variants C282Y, H63D, S65C was analyzed by PCR RFLP method among Beta Thalassemia Trait (BTT) (n = 203), Beta Thalassemia Major (BTM) (n = 19) and age and sex-matched control samples (n = 200). The present study furnished allele frequency of H63D variant in BTT, BTM and controls 8.13, 15.8 and 6% respectively. Ten out of 33 heterozygous H63D variants exhibited iron overload with higher ferritin levels indicating HFE variant might aggravate the absorption of iron. The C282Y variant was present in heterozygous state in 1 case among beta thalassemia carriers. The C282Y variant was absent among BTM and control cases. S65C HFE variant was absent in the present study. Iron overload was completely absent in the control cases among all three HFE genotypes. Hence it is inferred from the present investigation, analysis of HFE genes and iron status will remarkably help to reason out the probable reason behind the iron status and support in proper management of beta thalassemia cases.
- Hereditary Hemochromatosis,
- beta thalassemia,
- HFE,
- iron overload,
- ferritin
Citation: Bhuvana Selvaraj, Sangeetha Soundararajan, Shettu Narayanasamy, Ganesan Subramanian, Senthil Kumar Ramanathan. Frequency of hereditary hemochromatosis gene mutations and their effects on iron overload among beta thalassemia patients of Chennai residents[J]. AIMS Molecular Science, 2021, 8(4): 233-247. doi: 10.3934/molsci.2021018

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Abstract

Hereditary Hemochromatosis (HH) is an autosomal recessive disorder of iron metabolism associated with HFE gene mutations, characterized by increased iron absorption and accumulation leading to multi-organ damage caused by iron overload toxicity. Beta thalassemia is caused by a mutation in the human beta globin gene. Imbalanced production of globin chain results in beta thalassemia, where the unpaired alpha chains precipitates in red cell precursors leading to ineffective erythropoiesis and reduced RBC survival. Both HH and beta thalassemia condition results in rapid accumulation of iron lead to iron overload in tissues and organs. The study aims to analyze the frequency of HFE variants among beta thalassemia cases and their effect on iron overload. The frequency of three HFE variants C282Y, H63D, S65C was analyzed by PCR RFLP method among Beta Thalassemia Trait (BTT) (n = 203), Beta Thalassemia Major (BTM) (n = 19) and age and sex-matched control samples (n = 200). The present study furnished allele frequency of H63D variant in BTT, BTM and controls 8.13, 15.8 and 6% respectively. Ten out of 33 heterozygous H63D variants exhibited iron overload with higher ferritin levels indicating HFE variant might aggravate the absorption of iron. The C282Y variant was present in heterozygous state in 1 case among beta thalassemia carriers. The C282Y variant was absent among BTM and control cases. S65C HFE variant was absent in the present study. Iron overload was completely absent in the control cases among all three HFE genotypes. Hence it is inferred from the present investigation, analysis of HFE genes and iron status will remarkably help to reason out the probable reason behind the iron status and support in proper management of beta thalassemia cases.

Abbreviations

BTH

Beta Thalassemia Homozygous

BTM

Beta Thalassemia Major

BTT

Beta Thalassemia Trait

HBB

Hemoglobin Subunit Beta gene

Hereditary Hemochromatosis

SNPs

Single Nucleotide Polymorphism

Wild type allele

Acknowledgments

The authors thank HOD of Zoology, Principal, Pachaiyappa's college, Chennai, for their support. The authors are very grateful to the authorities of Hitech Diagnostic Centre, Kilpauk, Chennai for their support and valuable suggestions.

Conflict of interest

Authors declare no conflict of interest in this manuscript.

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